This study is a proposed extension of our efforts to understand the genetic regulation of morphogenesis. Specifically, we will carry out an indepth analysis of those genes which affect the basic body plan of Drosophila melanogaster. The loci chosen for analysis are those which cause homoeotic transformations and those which disrupt the actual pattern of segmentation. These genes can be viewed as selectors or switches which choose between alternate ontogenic pathways. As such, they represent the genetic regulatory elements which are responsible for the development of pattern and form from the single-celled zygote. The proposed analysis will be carried out on the Antennapedia gene complex (ANT-C) and those segment-disrupting mutations which interact with it. The ANT-C is a group of tightly linked loci which specify segmental identity in the anterior end of the embryo and adult. Mutations in these loci can be seen to transform head and anterior thoracic structures into more posteriorly located entities (e.g., antenna greater than leg). A large number of mutations in the loci of interest have been and will be generated. Their continued analysis by both genetic and developmental techniques will reveal the possible role(s) of the normal genes in development. We have recently augmented these more """"""""classical"""""""" approaches by cloning, in overlapping DNA fragments, the majority of the ANT-C. With these cloned probes, we have now begun an investigation of the gene products of the ANT-C. We believe that this more molecular approach when coupled with the developmental and genetic analysis will allow us to reach some truly insightful conclusions about the role of the homoeotic loci in development. We also propose to extend our analysis to include other species of Drosophila. Using the DNA clones, we will recover """"""""genes"""""""" homologous in sequence to the ANT-C from closely and more distantly related species of diptera. The structure, at the DNA level, of these loci and a test of their ability to function in D. melanogaster through transformation should allow us to determine these portions of the ANT-C, if any, which are the most critical to normal development.
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